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Targeting tumor neovasculature with modified chimeric antigen receptors

A chimeric antigen receptor and targeting moiety technology, which can be used in anti-tumor drugs, anti-receptor/cell surface antigen/cell surface determinant immunoglobulin, microorganisms, etc.

Inactive Publication Date: 2016-03-23
UNIV HOUSTON SYST
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

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Problems solved by technology

However, the ability of EPR to facilitate nanoparticle delivery to solid tumors remains controversial

Method used

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  • Targeting tumor neovasculature with modified chimeric antigen receptors
  • Targeting tumor neovasculature with modified chimeric antigen receptors
  • Targeting tumor neovasculature with modified chimeric antigen receptors

Examples

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Embodiment

[0055] cell line. Human umbilical vein endothelial cells (HUVEC) and the murine melanoma cell line B16-F0 were obtained from ATCC (Manassas, VA). HUVEC were cultured in Dulbecco's Modified Eagle's Medium (DMEM; Cat. No. 30-2002) formulated by ATCC containing 20% ​​fetal bovine serum (FBS), and B16-F0 cells were grown in a medium containing 100 μg / ml Streptomycin and 100U / ml penicillin in 10% FBSDMEM. B16-GFPluc cells were established in the inventor's laboratory by co-transfecting pIR-eGFP-luc and pCMV-piggyBac plasmids into B16-F0, followed by flow cytometry sorting and single cell cloning as described previously (FuX, et al., Asimple and sensitive method for measuring tumor-specific T cell cytotoxicity. PLoS One 2010; 5: e11867 (2010)).

[0056] Retroviral vector construction and preparation. The construction of the retroviral vector is schematically shown in Figure 1Amiddle. The coding sequence for Leu-28-serastatin (MECESGPCCRCKFLKEGTICKRARGDDLDDYCNGKTCDCPRNPHKGPAT; G...

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Abstract

A T cell transduced with a chimeric antigen receptor can be administered to a host to kill cancer cells. The chimeric antigen receptor can include a targeting moiety with a strong binding affinity to Alpha v Beta 3 integrin, including but not limited to an echistatin polypeptide. The targeting moiety can also be modified to have a reduced binding affinity to Alpha 5 Beta 1 integrin.

Description

[0001] Cross References to Related Applications [0002] This application claims priority to US Provisional Application No. 61 / 835,147, filed June 14, 2013, which is hereby incorporated by reference in its entirety. [0003] Government funding: [0004] NIH reference number R01CA132792. Background of the invention [0005] Several promising immunotherapies are currently being developed to fight cancer. For example, one type of immunotherapy exploits the predominance of antigen-specific T cells in cell-mediated immunity. T cells recognize their targets through the T cell receptor (TCR), which binds to antigenic peptides presented by the major histocompatibility complex (MHC) on the surface of cancer cells. In the presence of co-stimulatory molecules, this binding results in T cell activation and subsequent lysis of the bound target cells (VanderMerwePA, et al., Molecular interactions mediating Tcellantigenrecognition, Annu. Rev. Immunol. 21:659-84 (2003)). However, most tum...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): C07K16/30
CPCA61K38/195C12N2740/13043A61K45/06A61P35/00A61K2239/26A61K2239/31A61K39/4611A61K39/4631A61K39/464406A61K39/461A61K2300/00A61K35/17
Inventor 张小柳付新平
Owner UNIV HOUSTON SYST
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